Drug Loaded, Biodegradable Nerve Conduits for the SimultaneousChemical and Electrical Stimulation of Neural Cells as a TherapeuticApproach for Peripheral Nerve Regeneration

摘要

Restoring peripheral nerve trauma is an important research field in regenerative medicine. One therapeutical approach is to use tissue engineered nerve conduits consisting of biodegradable polymers. These materials can be designed to include active agents to further stimulate or influence proliferation, maturation, differentiation or migration of specific neuronal cell in these nerve guides. We have developed a method to electrically deposit and immobilize neuronal cells and extracellular matrix proteins on self structured micro electrodes.= These electrodes also present a feasible methodology to investigate electrical stimulation of nerve cells. In our approach, poly-D,L-lactideco-glycolides (PLGA) were investigated as possible substrate for these electrodes, while further allowing for the integration of model substances in a drug release concept. Ina first approach, caffeine was used due to its well known effect of both stimulating and inhibiting effects on certain neuronal cells, while also allowing easy incorporation into PLGA via chemical means. A Plackett-Burman experimental design was used to find the optimum composition among different parameters such as drug concentration, polymer concentration, type of solvent and film-drying condition. The optimized drug loaded polymer, films were tested for their release and degradation profile, and their behavior in cell culture.. Finally, we are currently establishing an integrated experimental setup, combining caffeine modified PLGA film substrates with the manufacturing of the electrode structures to investigate cell deposition via electrical means and stimulation/ inhibition via chemical release.